P2 promoter variants of the hepatocyte nuclear factor 4α gene are associated with type 2 diabetes in Mexican Americans

Donna M Lehman, Dawn K. Richardson, Chris P. Jenkinson, Kelly J. Hunt, Thomas D. Dyer, Robin J Leach, Rector Arya, Hanna E. Abboud, John Blangero, Ravindranath Duggirala, Michael P. Stern

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Abstract

Common and rare variants of the hepatocyte nuclear factor 4α (HNF4A) gene have been associated with type 2 diabetes and related traits in several populations suggesting the involvement of this transcription factor in diabetes pathogenesis. Single nucleotide polymorphisms (SNPs) within a large haplotype block surrounding the alternate P2 promoter, located ∼45 kb upstream from the coding region, have been investigated in several populations of varying ethnicity with inconsistent results. Additionally, SNPs located within the P1 promoter and coding region have also been inconsistently associated with type 2 diabetes. Characterization of variation across this gene region in Mexican-American populations has not been reported. We therefore examined polymorphisms across the HNF4A gene in a cohort of Mexican-American pedigrees and assessed their association with type 2 diabetes. We observed evidence for association of SNPs in the P2 promoter region with type 2 diabetes (P = 0.003) and its age at diagnosis (P = 0.003). The risk allele frequency (53%) was intermediate to that reported in Caucasian populations (20-27%) and Pima Indians (83%). No other SNPs were associated with either trait. These results support the possibility that a variant in the P2 promoter region of HNF4A, or variants in linkage disequilibrium within this region, contributes to susceptibility to type 2 diabetes in many ethnic populations including Mexican Americans.

Original languageEnglish (US)
Pages (from-to)513-517
Number of pages5
JournalDiabetes
Volume56
Issue number2
DOIs
StatePublished - Feb 2007

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Hepatocyte Nuclear Factor 4
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Genetic Promoter Regions
Population
Genes
Potassium Iodide
Linkage Disequilibrium
Pedigree
Gene Frequency
Haplotypes
Transcription Factors

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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P2 promoter variants of the hepatocyte nuclear factor 4α gene are associated with type 2 diabetes in Mexican Americans. / Lehman, Donna M; Richardson, Dawn K.; Jenkinson, Chris P.; Hunt, Kelly J.; Dyer, Thomas D.; Leach, Robin J; Arya, Rector; Abboud, Hanna E.; Blangero, John; Duggirala, Ravindranath; Stern, Michael P.

In: Diabetes, Vol. 56, No. 2, 02.2007, p. 513-517.

Research output: Contribution to journalArticle

Lehman, DM, Richardson, DK, Jenkinson, CP, Hunt, KJ, Dyer, TD, Leach, RJ, Arya, R, Abboud, HE, Blangero, J, Duggirala, R & Stern, MP 2007, 'P2 promoter variants of the hepatocyte nuclear factor 4α gene are associated with type 2 diabetes in Mexican Americans', Diabetes, vol. 56, no. 2, pp. 513-517. https://doi.org/10.2337/db06-0881
Lehman, Donna M ; Richardson, Dawn K. ; Jenkinson, Chris P. ; Hunt, Kelly J. ; Dyer, Thomas D. ; Leach, Robin J ; Arya, Rector ; Abboud, Hanna E. ; Blangero, John ; Duggirala, Ravindranath ; Stern, Michael P. / P2 promoter variants of the hepatocyte nuclear factor 4α gene are associated with type 2 diabetes in Mexican Americans. In: Diabetes. 2007 ; Vol. 56, No. 2. pp. 513-517.
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abstract = "Common and rare variants of the hepatocyte nuclear factor 4α (HNF4A) gene have been associated with type 2 diabetes and related traits in several populations suggesting the involvement of this transcription factor in diabetes pathogenesis. Single nucleotide polymorphisms (SNPs) within a large haplotype block surrounding the alternate P2 promoter, located ∼45 kb upstream from the coding region, have been investigated in several populations of varying ethnicity with inconsistent results. Additionally, SNPs located within the P1 promoter and coding region have also been inconsistently associated with type 2 diabetes. Characterization of variation across this gene region in Mexican-American populations has not been reported. We therefore examined polymorphisms across the HNF4A gene in a cohort of Mexican-American pedigrees and assessed their association with type 2 diabetes. We observed evidence for association of SNPs in the P2 promoter region with type 2 diabetes (P = 0.003) and its age at diagnosis (P = 0.003). The risk allele frequency (53{\%}) was intermediate to that reported in Caucasian populations (20-27{\%}) and Pima Indians (83{\%}). No other SNPs were associated with either trait. These results support the possibility that a variant in the P2 promoter region of HNF4A, or variants in linkage disequilibrium within this region, contributes to susceptibility to type 2 diabetes in many ethnic populations including Mexican Americans.",
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